aging Flashcards
average life expectancy
80 yrs. 77yrs for men, 82 yrs for women
What is the expected maximum life expectancy
85-90 yrs
define life span and the human life span
maximal life expectancy- for humans it is 110yrs but very few individuals reach this age
Normal Effects of Aging
•From the late twenties to ninety, there is a steady decline in the function of nearly every body system.
effects of aging on the brain
atrophy, 10% loss of volume between age 35 and 60 as indicated from brain scan data. Mainly due to loss of myelin. Some loss of subcortical nuclei in the gray matter. Often mild problems with cognition, memory
Effects of aging on lung
loss of elastic tissue. Accumulation of anthracotic pigment (especially for city dwellers), often very mild emphysematous changes
aging of hematopoietic system
•atrophy of spleen, thymus and bone marrow.
aging of soft tissue
increase in body fat
aging of kidneys
loss of nephrons
aging of heart and liver
accumulation of lipofuscin, the so-called “wear and tear” pigment- a product of the peroxidation of unsaturated fatty acids.
aging of blood vessels
Generalized atherosclerosis, varicosities are common
diseases associated with aging
- cancer- most deaths occur around age 70. carcinoma is dz of advanding age. 2. atherosclerosis. 3. Strokes. 4.diabetes- non insulin dependent. 5. thromboembolism. 6. Parkinsons and Alzheimers.
theories of aging
- the clock theory- the aging process and death are programmed in the same way that early development is programmed. Aging is controlled by aging genes.. 2. the rust theory- aging results from the accumulation over time of oxidative damage to cells and tissues
Evidence for the clock theory
- Somatic cells are “programmed” to die after they have undergone a set number of cell divisions. Fibroblasts from old adults may senesce after only 10 to 20 doublings (compared to 80 doublings in fetus). 2. there are human genetic conditions that cause premature aging. 3. longevity runs in families. 4. genes that affect life span have been identified in some animals
What causes somatic cells to senesce
Telomeres which help stabilize chromosome ends and are needed for faithful chromosome segregation are shortened each cell division.
Telomerase complex
Catalytically adds TTAGGG to 3’ end of telomere of the leading strand
telomerase diseases
- aplastic anemia- mutation in telomerase reverse transcriptase. 2. bone marrow failure- mutations in TERC. 3. Dyskeratosis congenta- skin hyperpigmentation, oral leukoplakia, dystrophic nails—bone marrow failure, pul/liver fibrosis are all due to mutations in Dyskerin
Progeria
Mutation in Lamin A gene. rare, affected individuals age at an accelerated rate, life span is only agout 10 years. Death usually from cardiac or cerebrovascular disease.
function of Lamin A gene/protein
Lamin A is an intermediate filament present in the nucleus. It forms part of the apparatus that tethers the chromosome to the nuclear envelope.
Werners syndrome
affected patients show signs of aging in their early twenties- develop cataracts, aging changes in skin and hair. Early onset of cancer and heart disease- death by age 50. Mutation is in the gene for DNA helicase- defect in repair of DNA damage
Mutations that increase longevity in C. elegans (nematodes)
1.Age-1 gene- mutation inactivates a phosphatidylinositol 3-kinase 2. Insulin-like growth factor receptor gene mutations. 3. Clk -1 gene– encodes an enzyme that helps synthesize coenzyme Q, a component of the mitochondrial respiratory chain. 4. Sir2– encodes a histone deacetylase that promotes gene “silencing”. Overproduction increases longevity. Stabilizers rDNA genes in nucleolus.
Evidence for oxidation theory of aging
- lipofuscin, cross linked collagen and oxidized DNA/ protein build up. 2. Restricting calories (and lowering metabolic rate) increases longevity by 30-50%. 3. increased somatic mutations in mitochondrial DNA
What causes mutations in mitochondrial DNA to build up over time?
MtDNA sustains a high rate of oxidative injury because of its location and from the fact that it can not be repaired very well. The accumulation of mutations in MtDNA in somatic tissues may be what causes the well documented decline in oxidative phosphorylation that occurs as we age.
List the molecules that favor aging when activated
GH, IGF-1, (growth pathways) P13K, Akt, mTOR (nutrition sensing)
List the molecules with anti-aging properties
FOXO, PTEN, AMPK, Sirt1, PGC-1a. Inhibition of mTOR is antiaging and mimics caloric restriction
rapamycin
inhibits mTOR, extending lifespan
